Original Paper Received: May 1, 2014 Accepted after revision: July 25, 2014 Published online: January 21, 2015
Fetal Diagn Ther 2015;37:301–304 DOI: 10.1159/000366158
Prenatal Diagnosis of Open Spina Bifida in Emilia-Romagna Tullio Ghi a Guido Cocchi b Letizia Conti b Giuseppina Pacella a Aly Youssef a Nicola Rizzo a Gianluigi Pilu a
Departments of a Obstetrics and Gynecology and b Neonatology, Sant’Orsola Malpighi University Hospital, University of Bologna, Bologna, Italy
Key Words Spina bifida · Neural tube defect · Prenatal diagnosis
Abstract Objective: To report recent data on the epidemiology of pregnancies affected by open spina bifida in the EmiliaRomagna region of Italy. Methods: All cases of open spina bifida diagnosed in the Emilia-Romagna region between 2001 and 2011 and reported to the IMER regional registry were included in the study group. The pregnancy outcome was retrospectively assessed. Results: In the study period out of 390,978 babies born in Emilia-Romagna 126 cases of open spina bifida were reported to the IMER registry, resulting in a global prevalence of 3.2 per 10,000 births. Prenatal diagnosis was achieved in the vast majority of these cases (105/126; 83.3%) and in a great proportion of those women (85/105; 80.9%) who opted for termination of pregnancy. Conclusions: In a wide region of northern Italy where ultrasound anomaly scan is routinely offered to the general population, the vast majority of cases of open spina bifida are diagnosed antenatally and terminated electively. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 1015–3837/15/0374–0301$39.50/0 E-Mail [email protected] www.karger.com/fdt
Introduction
Spina bifida is a common malformation of the central nervous system, which results from failure of closure of the neural tube with consequent exposure of the neural canal content during the early period of embryonic development. Spina bifida is a broad term that encompasses several defects variable in anatomy and severity, including myelomeningocele, meningocele, and lipomeningocele. Among these, the myelomeningocele (protrusion of the nervous tissue and its covering through a defect in the vertebrae and skin) represents by far the most common type, accounting for about 90% of spina bifida cases [1, 2]. Its incidence is reported to range from 2 to 20 per 10,000 births according to different geographic areas, being higher in the United Kingdom (from 5.9 to 13.1 per 10,000 births) and Asia (10.6 per 10,000 births) and lower in the United States (from 3.1 per 10,000 births) and in the other European countries (from 2.0 to 10.5 per 10,000 births) [3–7]. The causes of spina bifida are multifactorial, including genetic predisposition, environmental factors and maternal conditions [8]. In the past the diagnosis of open spina bifida was done prenatally by maternal serum alphafetoprotein (AFP) screening [9, 10] combined Dr. Tullio Ghi, MD, PhD Department of Obstetrics and Gynecology S. Orsola-Malpighi University Hospital Via Massarenti, 13, IT–40138 Bologna (Italy) E-Mail tullioghi @ yahoo.com
with ultrasound diagnostic criteria [11–14]. In the last few years antenatal diagnosis is almost exclusively based upon sonographic findings [15]. We herein report recent data on the prevalence, prenatal diagnosis and termination of pregnancy in pregnancies affected by open spina bifida in the Emilia-Romagna region of Italy.
Material and Methods This was a retrospective survey conducted in Emilia-Romagna, a wide region of Northern Italy with about 4 million inhabitants and 40,000 pregnancies per year. The Emilia-Romagna Registry of Congenital Malformations (IMER; www.registroimer.it) was founded in 1978, covers all birth centers in the region, and is a full member of the EUROCAT registry (European surveillance of congenital anomalies; www.eurocat-network.eu). The IMER registry was searched to identify all new infants born and diagnosed with open spina bifida from 2001 to 2011. Epidemiology, antenatal detection rate and pregnancy outcome of all cases of isolated open spina bifida (livebirth, stillbirth and elective termination of pregnancy) was assessed. In Italy termination of pregnancy due to fetal anomaly is allowed within 23 weeks of gestation. We deliberately excluded cases of closed spina bifida (including spina bifida occulta) as prenatal and postnatal classification of these forms is poorly reproducible. Furthermore, cases of spina bifida associated with other CNS or extra CNS anomalies were also excluded from our study group. In Emilia-Romagna all patients are offered an ultrasound anomaly scan at 20–21 weeks of gestation. At mid-trimester ultrasound, the following fetal structures are thoroughly examined and described in the report in accordance with the SIEOG guidelines issued in 1996 and modified in 2006: the width of the distal cerebral lateral ventricle; the transverse diameter of the cerebellum; the integrity of the spine on the sagittal or the axial plane. An expert anomaly scan in a referral centre of prenatal medicine is offered to pregnant women with an increased level of AFP (>2.5 MoM) on maternal serum or on amniotic fluid or to those with a previous child affected by open neural tube defect. In Emilia-Romagna, the triple test including the measurement of the serum alphafeto protein at 16 weeks was commonly performed as the main screening for chromosomal anomalies until 2005. This policy was cancelled and replaced by the combined test at 11–13 weeks from 2005 onward. A sonographic diagnosis of open spina bifida is based upon the following criteria: discontinuity of the line delineating the fetal spine in the sagittal and axial plane in association with intracranial signs. The latter included frontal bone scalloping (lemon sign) and obliteration of the cisterna magna, with abnormal shape of the cerebellum (banana sign) [15]. Cases with sonographic appearance of a cystic mass bulging from the back but without cranial signs are classified as closed spina bifida [15] and as mentioned earlier were not included in our study population. For all cases where termination of pregnancy or abortion/death occurred after 16 weeks of gestation, the final diagnosis of open spina bifida was based upon the postmortem examination. No data
302
Fetal Diagn Ther 2015;37:301–304 DOI: 10.1159/000366158
Table 1. Open spina bifida 2001–2011 IMER registry
Year
Live
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
Total births
Total ratea (×10,000)
Stillbirths
ToP
2 1 3 6 4 2 2 3 6 5 5
0 0 0 0 0 1 0 0 1 0 0
5 9 10 15 7 8 6 7 10 2 6
23,670 26,010 27,412 27,962 37,605 39,847 40,662 42,397 42,772 42,154 40,487
2.96 3.84 4.74 7.51 2.92 2.76 1.97 2.36 3.97 1.66 2.71
39
2
85
390,978
3.22
ToP = Termination of pregnancies. a p = 0.021 (linear-by-linear χ2 test).
on the prevalence of spina bifida were available for feticide or miscarriage occurring prior to 16 weeks of gestation. No information about the use of additional examination such as X-ray was given on the registry. Statistics The prevalence of open spina bifida was estimated across the study period as the number of affected cases divided by the total number of births. Mean, standard deviation and absolute and relative frequencies were reported as descriptive statistics. The data were analyzed by means of the linear-by-linear chisquare and the Fisher’s exact tests by running the IBM SPSS Statistics package (Version 21) on a personal computer. Two-tailed p values
Fetal Diagn Ther 2015;37:301–304 DOI: 10.1159/000366158
Prenatal Diagnosis of Open Spina Bifida in Emilia-Romagna Tullio Ghi a Guido Cocchi b Letizia Conti b Giuseppina Pacella a Aly Youssef a Nicola Rizzo a Gianluigi Pilu a
Departments of a Obstetrics and Gynecology and b Neonatology, Sant’Orsola Malpighi University Hospital, University of Bologna, Bologna, Italy
Key Words Spina bifida · Neural tube defect · Prenatal diagnosis
Abstract Objective: To report recent data on the epidemiology of pregnancies affected by open spina bifida in the EmiliaRomagna region of Italy. Methods: All cases of open spina bifida diagnosed in the Emilia-Romagna region between 2001 and 2011 and reported to the IMER regional registry were included in the study group. The pregnancy outcome was retrospectively assessed. Results: In the study period out of 390,978 babies born in Emilia-Romagna 126 cases of open spina bifida were reported to the IMER registry, resulting in a global prevalence of 3.2 per 10,000 births. Prenatal diagnosis was achieved in the vast majority of these cases (105/126; 83.3%) and in a great proportion of those women (85/105; 80.9%) who opted for termination of pregnancy. Conclusions: In a wide region of northern Italy where ultrasound anomaly scan is routinely offered to the general population, the vast majority of cases of open spina bifida are diagnosed antenatally and terminated electively. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 1015–3837/15/0374–0301$39.50/0 E-Mail [email protected] www.karger.com/fdt
Introduction
Spina bifida is a common malformation of the central nervous system, which results from failure of closure of the neural tube with consequent exposure of the neural canal content during the early period of embryonic development. Spina bifida is a broad term that encompasses several defects variable in anatomy and severity, including myelomeningocele, meningocele, and lipomeningocele. Among these, the myelomeningocele (protrusion of the nervous tissue and its covering through a defect in the vertebrae and skin) represents by far the most common type, accounting for about 90% of spina bifida cases [1, 2]. Its incidence is reported to range from 2 to 20 per 10,000 births according to different geographic areas, being higher in the United Kingdom (from 5.9 to 13.1 per 10,000 births) and Asia (10.6 per 10,000 births) and lower in the United States (from 3.1 per 10,000 births) and in the other European countries (from 2.0 to 10.5 per 10,000 births) [3–7]. The causes of spina bifida are multifactorial, including genetic predisposition, environmental factors and maternal conditions [8]. In the past the diagnosis of open spina bifida was done prenatally by maternal serum alphafetoprotein (AFP) screening [9, 10] combined Dr. Tullio Ghi, MD, PhD Department of Obstetrics and Gynecology S. Orsola-Malpighi University Hospital Via Massarenti, 13, IT–40138 Bologna (Italy) E-Mail tullioghi @ yahoo.com
with ultrasound diagnostic criteria [11–14]. In the last few years antenatal diagnosis is almost exclusively based upon sonographic findings [15]. We herein report recent data on the prevalence, prenatal diagnosis and termination of pregnancy in pregnancies affected by open spina bifida in the Emilia-Romagna region of Italy.
Material and Methods This was a retrospective survey conducted in Emilia-Romagna, a wide region of Northern Italy with about 4 million inhabitants and 40,000 pregnancies per year. The Emilia-Romagna Registry of Congenital Malformations (IMER; www.registroimer.it) was founded in 1978, covers all birth centers in the region, and is a full member of the EUROCAT registry (European surveillance of congenital anomalies; www.eurocat-network.eu). The IMER registry was searched to identify all new infants born and diagnosed with open spina bifida from 2001 to 2011. Epidemiology, antenatal detection rate and pregnancy outcome of all cases of isolated open spina bifida (livebirth, stillbirth and elective termination of pregnancy) was assessed. In Italy termination of pregnancy due to fetal anomaly is allowed within 23 weeks of gestation. We deliberately excluded cases of closed spina bifida (including spina bifida occulta) as prenatal and postnatal classification of these forms is poorly reproducible. Furthermore, cases of spina bifida associated with other CNS or extra CNS anomalies were also excluded from our study group. In Emilia-Romagna all patients are offered an ultrasound anomaly scan at 20–21 weeks of gestation. At mid-trimester ultrasound, the following fetal structures are thoroughly examined and described in the report in accordance with the SIEOG guidelines issued in 1996 and modified in 2006: the width of the distal cerebral lateral ventricle; the transverse diameter of the cerebellum; the integrity of the spine on the sagittal or the axial plane. An expert anomaly scan in a referral centre of prenatal medicine is offered to pregnant women with an increased level of AFP (>2.5 MoM) on maternal serum or on amniotic fluid or to those with a previous child affected by open neural tube defect. In Emilia-Romagna, the triple test including the measurement of the serum alphafeto protein at 16 weeks was commonly performed as the main screening for chromosomal anomalies until 2005. This policy was cancelled and replaced by the combined test at 11–13 weeks from 2005 onward. A sonographic diagnosis of open spina bifida is based upon the following criteria: discontinuity of the line delineating the fetal spine in the sagittal and axial plane in association with intracranial signs. The latter included frontal bone scalloping (lemon sign) and obliteration of the cisterna magna, with abnormal shape of the cerebellum (banana sign) [15]. Cases with sonographic appearance of a cystic mass bulging from the back but without cranial signs are classified as closed spina bifida [15] and as mentioned earlier were not included in our study population. For all cases where termination of pregnancy or abortion/death occurred after 16 weeks of gestation, the final diagnosis of open spina bifida was based upon the postmortem examination. No data
302
Fetal Diagn Ther 2015;37:301–304 DOI: 10.1159/000366158
Table 1. Open spina bifida 2001–2011 IMER registry
Year
Live
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
Total births
Total ratea (×10,000)
Stillbirths
ToP
2 1 3 6 4 2 2 3 6 5 5
0 0 0 0 0 1 0 0 1 0 0
5 9 10 15 7 8 6 7 10 2 6
23,670 26,010 27,412 27,962 37,605 39,847 40,662 42,397 42,772 42,154 40,487
2.96 3.84 4.74 7.51 2.92 2.76 1.97 2.36 3.97 1.66 2.71
39
2
85
390,978
3.22
ToP = Termination of pregnancies. a p = 0.021 (linear-by-linear χ2 test).
on the prevalence of spina bifida were available for feticide or miscarriage occurring prior to 16 weeks of gestation. No information about the use of additional examination such as X-ray was given on the registry. Statistics The prevalence of open spina bifida was estimated across the study period as the number of affected cases divided by the total number of births. Mean, standard deviation and absolute and relative frequencies were reported as descriptive statistics. The data were analyzed by means of the linear-by-linear chisquare and the Fisher’s exact tests by running the IBM SPSS Statistics package (Version 21) on a personal computer. Two-tailed p values
